Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation

Harsh R. Desai, Tharini Sivasubramaniyam, Xavier S. Revelo, Stephanie A. Schroer, Cynthia T. Luk, Prashanth R. Rikkala, Adam H. Metherel, David W. Dodington, Yoo Jin Park, Min Jeong Kim, Joshua A. Rapps, Rickvinder Besla, Clinton S. Robbins, Kay Uwe Wagner, Richard P. Bazinet, Daniel A. Winer, Minna Woo

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


During obesity, macrophages can infiltrate metabolic tissues, and contribute to chronic low-grade inflammation, and mediate insulin resistance and diabetes. Recent studies have elucidated the metabolic role of JAK2, a key mediator downstream of various cytokines and growth factors. Our study addresses the essential role of macrophage JAK2 in the pathogenesis to obesity-associated inflammation and insulin resistance. During high-fat diet (HFD) feeding, macrophage-specific JAK2 knockout (M-JAK2-/-) mice gained less body weight compared to wildtype littermate control (M-JAK2+/+) mice and were protected from HFD-induced systemic insulin resistance. Histological analysis revealed smaller adipocytes and qPCR analysis showed upregulated expression of some adipogenesis markers in visceral adipose tissue (VAT) of HFD-fed M-JAK2-/- mice. There were decreased crown-like structures in VAT along with reduced mRNA expression of some macrophage markers and chemokines in liver and VAT of HFD-fed M-JAK2-/- mice. Peritoneal macrophages from M-JAK2-/- mice and Jak2 knockdown in macrophage cell line RAW 264.7 also showed lower levels of chemokine expression and reduced phosphorylated STAT3. However, leptin-dependent effects on augmenting chemokine expression in RAW 264.7 cells did not require JAK2. Collectively, our findings show that macrophage JAK2 deficiency improves systemic insulin sensitivity and reduces inflammation in VAT and liver in response to metabolic stress.

Original languageEnglish (US)
Article number7653
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

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